1. Field of the Invention
The present invention relates to a method of producing 2-alkyl-3-aminothiophne, and intermediates for producing the same.
2. Description of the Related Art
As a method of producing 2-alkyl-3-aminothiophene, a method of reacting a 3-aminothiophene derivative with a carbonyl compound to produce a 2-alkenyl-3-aminothiophene derivative, and then reducing the same, is disclosed (for example, refer to Japanese Patent Application Laid-Open (JP-A) No. 2008-120710).
Further, as a method of producing 2-alkyl-3-mitrothiophene, a method of reacting 3-nitrothiophene with a Grignard reagent, and then oxidizing the same, is disclosed (for examples, refer to Tetrahedron, Vol. 44, No. 20, (1988), p. 6435).
Moreover, as a method of producing 3-nitrothiophene, a method of nitrating thiophene is disclosed (for example, refer to Justus Liebigs Annalen der Chemie, Vol. 501, (1933), p. 174).
However, due to the instable nature of a 3-aminothiophene derivative and the difficulty in handling the same, the method described in Japanese Patent Application Laid-Open (JP-A) No. 2008-120710 requires a process of attaching/removing a protective group for the amino group, such as an acyl group or a carbamate group. Therefore, the method is still to be improved in terms of operability and cost efficiency.
On the other hand, since it is known that a nitro group can be converted to an amino group through a reduction reaction, as represented by catalytic hydrogenation, it is expected that a 3-amino-2-allylthiophene derivative can be produced by reducing a 2-alkyl-3-nitrothiophene derivative. However, due to the difficulty in producing the 3-alkyl-2-nitrothiophene derivative, no reports have been made concerning the method of producing a 2-alkyl-3-aminothiophene derivative by reducing a 2-alkyl-3-nitrothiophene derivative.
In the method of producing 2-alkyl-3-nitrothiophene described in Tetrahedron, Vol. 44, No. 20, (1988), p. 6435, there is room for improvement in that the production of 3-nitrothiophene, which is a starting material used in this method, is difficult.
In the method described in Justus Liebigs Annalen der Chemie, Vol. 501, (1933), p. 174, the yield of the resulting product is low since it is obtained as a mixture of position isomers, and a process of separating these isomers is necessary. Therefore, the method is still to be improved in terms of operability and cost efficiency.